Embedded in the roughly 20,000 genes that make up the human genome are fragments of viral DNA, remnants of viral infections that afflicted primate ancestors millions of years ago.
These ancient segments of DNA, called endogenous retroviruses, were once thought to be harmless and inactive, just “junk” DNA.
However, recent research from the University of Colorado at Boulder reveals that these retroviruses can be reactivated and play a critical role in promoting cancer growth and survival.
The study also suggests that targeting and silencing specific endogenous retroviruses could increase the effectiveness of cancer treatments.
“Our study shows that today’s diseases can be significantly influenced by these ancient viral infections, which until recently received little attention from researchers,” said lead author Edward Chuong, assistant professor of molecular, cellular and developmental biology at CU Boulder.
An integral part of the human genome
Research shows that about 8% of the human genome consists of endogenous retroviruses that are integrated into the cells of our evolutionary ancestors, encouraging them to replicate and transmit their genetic material.
Over generations, these retroviruses have infiltrated sperm, eggs and embryos, anchoring their DNA as a fossil record and influencing evolutionary processes.
Although they can no longer produce functional viruses, Chuong’s research has shown that endogenous retroviruses can act as “switches” to activate nearby genes. Some have played a role in the development of the placenta, a key event in human evolution, and in the immune response to current viruses such as COVID-19.
“There has been a lot of work showing that these endogenous retroviruses can be domesticated for our benefit, but not much showing how they can harm us,” Chuong noted.
The role of viral DNA in cancer growth
To investigate their impact on cancer, Chuong and Atma Ivancevic, a research associate in his lab, examined genomic data from 21 types of human cancers using publicly available datasets.
Their research revealed that a particular lineage of endogenous retrovirus called LTR10, which infected some primates about 30 million years ago, showed unexpectedly high levels of activity in various cancers, such as lung and colon cancer. Further analysis of tumors from many colorectal cancer patients showed that LTR10 was active in about one-third of cases.
By using CRISPR to remove or silence sequences where LTR10 was present, the team found that critical genes supporting cancer development and growth were also disabled.
“We saw that when you silence this retrovirus in cancer cells, the proximity of gene expression is turned off,” Ivančević explained.
“We know that cancer cells express a lot of genes that shouldn’t be turned on, but nobody really knows what turns them on,” Chuong said. “It turns out that many of the switches that turn them on are derived from these ancient viruses.”
Other health problems
Interestingly, the endogenous retrovirus examined in their study appears to activate genes within the MAP-kinase pathway, a well-known cellular pathway that is often dysregulated in many cancers.
The study suggests that existing drugs called MAP-kinase inhibitors may work in part by deactivating an endogenous retroviral switch.
According to the authors, this single family of retroviruses regulates up to 70 cancer-related genes in the MAP-kinase pathway. Different retroviral lineages likely affect different pathways and promote different types of cancer.
Chuong theorizes that as individuals age, their genomic defenses deteriorate, allowing ancient viruses to reactivate and potentially contribute to other health problems as well.
This study was published in Scientific advances.
ABOUT THE EDITORIAL
Srishti Gupta Srishti studied English literature at Delhi University and has since realized that it is not her cup of tea. She has been an editor in every area and type of content imaginable, from children’s books to magazine articles. She enjoys popular culture, reading contemporary fiction and nonfiction, crafts, and spending time with her cats. With a keen interest in science, Srishti is particularly drawn to beats related to medicine, sustainability, genetic studies and anything related to biology.